A0A0B4K692 · NEP2_DROME
- ProteinNeprilysin-2
- GeneNep2
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids774 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Metalloendoprotease which cleaves peptides such as tachykinin peptide TK-2 at the amino side of hydrophobic residues (PubMed:15554877, PubMed:17157960).
Functions in female fertility, embryogenesis and memory formation (PubMed:24395329, PubMed:27629706).
Required in females for normal patterns of egg laying, probably due to its function in sperm retention and preventing sperm displacement by rival ejaculates (PubMed:24395329).
Also required for normal patterns of hatching due to its important role in early embryonic development (PubMed:24395329).
Required in the dorsal paired medial neurons for the proper formation of middle-term memory (PubMed:27629706).
Also required in the mushroom body neurons where it functions redundantly with neprilysins Nep3 and Nep4 in normal long-term memory formation (PubMed:27629706).
Functions in female fertility, embryogenesis and memory formation (PubMed:24395329, PubMed:27629706).
Required in females for normal patterns of egg laying, probably due to its function in sperm retention and preventing sperm displacement by rival ejaculates (PubMed:24395329).
Also required for normal patterns of hatching due to its important role in early embryonic development (PubMed:24395329).
Required in the dorsal paired medial neurons for the proper formation of middle-term memory (PubMed:27629706).
Also required in the mushroom body neurons where it functions redundantly with neprilysins Nep3 and Nep4 in normal long-term memory formation (PubMed:27629706).
Catalytic activity
Cofactor
Note: Binds 1 zinc ion per subunit.
pH Dependence
Optimum pH is 7-7.5 at 35 degrees Celsius.
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | extracellular space | |
Cellular Component | membrane | |
Cellular Component | plasma membrane | |
Molecular Function | endopeptidase activity | |
Molecular Function | metal ion binding | |
Molecular Function | metalloendopeptidase activity | |
Molecular Function | metallopeptidase activity | |
Biological Process | protein processing | |
Biological Process | proteolysis | |
Biological Process | sperm competition |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameNeprilysin-2
- EC number
- Cleaved into 1 chains
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Metazoa > Ecdysozoa > Arthropoda > Hexapoda > Insecta > Pterygota > Neoptera > Endopterygota > Diptera > Brachycera > Muscomorpha > Ephydroidea > Drosophilidae > Drosophila > Sophophora
Accessions
- Primary accessionA0A0B4K692
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Single-pass type II membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-20 | Cytoplasmic | ||||
Sequence: MQTVIQNPNWWRRRNKLEKS | ||||||
Transmembrane | 21-41 | Helical; Signal-anchor for type II membrane protein | ||||
Sequence: LLVSLGIMFVVLATGFGLWIG | ||||||
Topological domain | 42-774 | Extracellular | ||||
Sequence: KVLRTSPPSNPQATALHGDSTTINQVPTGTASKGKSGDSGDVCLTQECIHTASTVLRKMKPEVEPCDNFYEFACGTYLEEENIPDDKVSISTFSVISDKLQEQLKDIITAERPETEPKHFRLPNLLYKACMNKTLIETLGPEPITRVAERLGGWPLIKGDSWNADDSWTWQEQVKKFRTAGFSMDYIIDFSIGVDLQNSTKRLIDLDQSSLALSREYLVKGFNETLVTAYYKYMVDIAVLFGANRDLAKTELLLSLEFEMALANISWPNEKRRNSSELYNLRTPAQLQAAYPYVQWVDYMNALLPEGLNVAEDEMINLSVPSFFEDLGKLLAKTPKRVIANYMFWRIHGFSVGFLSEEFRKRQLQYATALSGRQEQEARWKECVDIATSSMDEVCEDDFDSLGISVGSLYVGKHFHKDSKANALEMVNEIRNVFNDILDEVNWMDAKTKKEAKLKLHSMATHIGYPDEMLDNEKLAAYYAKLDIDPDKYFESFLGMNIFGTDYSFNKLRLPVNKTDWVRHARPAIVNAFYSSLENSIQFPAGILQGHFFNAQRPKYMNFGAIGYVIGHEITHGFDDQGRQFDVKGNLRDWWHPDTQKAYLAKAKCIIEQYGNYTERATGLNLNGINTQGENIADNGGVKESYIAYRRWAEKHGPEAKLPGLDYTPEQMFWVAAGQTWCAKYRKESLKMRITTGVHSPSEFRVLGSLSNMKDFAKDFHCPEGSPMNPVQKCEVW |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
RNAi-mediated knockdown in females mated to wild-type males results in laying of fewer eggs due to impaired sperm retention and increased sperm displacement by rival ejaculates (PubMed:24395329).
Females also show a reduced hatch rate and only 20% of their progeny reach the adult stage (PubMed:24395329).
Unhatched eggs are fertilized but contain a clear polar body rosette instead of an embryo, suggesting that the eggs activate and complete meiosis but then embryogenesis is arrested (PubMed:24395329).
Wild-type females mated to males that undergo RNAi-mediated knockdown, display a slight reduction in fertility but lay the same number of eggs and have the same hatch rate as those mated to wild-type males (PubMed:24395329).
RNAi-mediated knockdown in the dorsal paired medial neurons impairs middle-term memory (MTM), but has no effect on long-term memory (LTM) formation, normal aversion learning and anesthesia-resistant memory (ARM) (PubMed:27629706).
RNAi-mediated knockdown in all mushroom body neurons has no effect on learning, ARM and LTM (PubMed:27629706).
However, simultaneous knockdown with Nep3 does impair LTM, and simultaneous knockdown with both Nep3 and Nep4 results in a further reduction in LTM formation (PubMed:27629706).
Simultaneous knockdown with only Nep4 has no effect on LTM formation (PubMed:27629706).
Females also show a reduced hatch rate and only 20% of their progeny reach the adult stage (PubMed:24395329).
Unhatched eggs are fertilized but contain a clear polar body rosette instead of an embryo, suggesting that the eggs activate and complete meiosis but then embryogenesis is arrested (PubMed:24395329).
Wild-type females mated to males that undergo RNAi-mediated knockdown, display a slight reduction in fertility but lay the same number of eggs and have the same hatch rate as those mated to wild-type males (PubMed:24395329).
RNAi-mediated knockdown in the dorsal paired medial neurons impairs middle-term memory (MTM), but has no effect on long-term memory (LTM) formation, normal aversion learning and anesthesia-resistant memory (ARM) (PubMed:27629706).
RNAi-mediated knockdown in all mushroom body neurons has no effect on learning, ARM and LTM (PubMed:27629706).
However, simultaneous knockdown with Nep3 does impair LTM, and simultaneous knockdown with both Nep3 and Nep4 results in a further reduction in LTM formation (PubMed:27629706).
Simultaneous knockdown with only Nep4 has no effect on LTM formation (PubMed:27629706).
PTM/Processing
Features
Showing features for chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000441991 | ?-774 | Neprilysin-2, soluble form | |||
Sequence: MQTVIQNPNWWRRRNKLEKSLLVSLGIMFVVLATGFGLWIGKVLRTSPPSNPQATALHGDSTTINQVPTGTASKGKSGDSGDVCLTQECIHTASTVLRKMKPEVEPCDNFYEFACGTYLEEENIPDDKVSISTFSVISDKLQEQLKDIITAERPETEPKHFRLPNLLYKACMNKTLIETLGPEPITRVAERLGGWPLIKGDSWNADDSWTWQEQVKKFRTAGFSMDYIIDFSIGVDLQNSTKRLIDLDQSSLALSREYLVKGFNETLVTAYYKYMVDIAVLFGANRDLAKTELLLSLEFEMALANISWPNEKRRNSSELYNLRTPAQLQAAYPYVQWVDYMNALLPEGLNVAEDEMINLSVPSFFEDLGKLLAKTPKRVIANYMFWRIHGFSVGFLSEEFRKRQLQYATALSGRQEQEARWKECVDIATSSMDEVCEDDFDSLGISVGSLYVGKHFHKDSKANALEMVNEIRNVFNDILDEVNWMDAKTKKEAKLKLHSMATHIGYPDEMLDNEKLAAYYAKLDIDPDKYFESFLGMNIFGTDYSFNKLRLPVNKTDWVRHARPAIVNAFYSSLENSIQFPAGILQGHFFNAQRPKYMNFGAIGYVIGHEITHGFDDQGRQFDVKGNLRDWWHPDTQKAYLAKAKCIIEQYGNYTERATGLNLNGINTQGENIADNGGVKESYIAYRRWAEKHGPEAKLPGLDYTPEQMFWVAAGQTWCAKYRKESLKMRITTGVHSPSEFRVLGSLSNMKDFAKDFHCPEGSPMNPVQKCEVW | ||||||
Chain | PRO_0000441990 | 1-774 | Neprilysin-2 | |||
Sequence: MQTVIQNPNWWRRRNKLEKSLLVSLGIMFVVLATGFGLWIGKVLRTSPPSNPQATALHGDSTTINQVPTGTASKGKSGDSGDVCLTQECIHTASTVLRKMKPEVEPCDNFYEFACGTYLEEENIPDDKVSISTFSVISDKLQEQLKDIITAERPETEPKHFRLPNLLYKACMNKTLIETLGPEPITRVAERLGGWPLIKGDSWNADDSWTWQEQVKKFRTAGFSMDYIIDFSIGVDLQNSTKRLIDLDQSSLALSREYLVKGFNETLVTAYYKYMVDIAVLFGANRDLAKTELLLSLEFEMALANISWPNEKRRNSSELYNLRTPAQLQAAYPYVQWVDYMNALLPEGLNVAEDEMINLSVPSFFEDLGKLLAKTPKRVIANYMFWRIHGFSVGFLSEEFRKRQLQYATALSGRQEQEARWKECVDIATSSMDEVCEDDFDSLGISVGSLYVGKHFHKDSKANALEMVNEIRNVFNDILDEVNWMDAKTKKEAKLKLHSMATHIGYPDEMLDNEKLAAYYAKLDIDPDKYFESFLGMNIFGTDYSFNKLRLPVNKTDWVRHARPAIVNAFYSSLENSIQFPAGILQGHFFNAQRPKYMNFGAIGYVIGHEITHGFDDQGRQFDVKGNLRDWWHPDTQKAYLAKAKCIIEQYGNYTERATGLNLNGINTQGENIADNGGVKESYIAYRRWAEKHGPEAKLPGLDYTPEQMFWVAAGQTWCAKYRKESLKMRITTGVHSPSEFRVLGSLSNMKDFAKDFHCPEGSPMNPVQKCEVW | ||||||
Disulfide bond | 84↔89 | |||||
Sequence: CLTQEC | ||||||
Disulfide bond | 107↔759 | |||||
Sequence: CDNFYEFACGTYLEEENIPDDKVSISTFSVISDKLQEQLKDIITAERPETEPKHFRLPNLLYKACMNKTLIETLGPEPITRVAERLGGWPLIKGDSWNADDSWTWQEQVKKFRTAGFSMDYIIDFSIGVDLQNSTKRLIDLDQSSLALSREYLVKGFNETLVTAYYKYMVDIAVLFGANRDLAKTELLLSLEFEMALANISWPNEKRRNSSELYNLRTPAQLQAAYPYVQWVDYMNALLPEGLNVAEDEMINLSVPSFFEDLGKLLAKTPKRVIANYMFWRIHGFSVGFLSEEFRKRQLQYATALSGRQEQEARWKECVDIATSSMDEVCEDDFDSLGISVGSLYVGKHFHKDSKANALEMVNEIRNVFNDILDEVNWMDAKTKKEAKLKLHSMATHIGYPDEMLDNEKLAAYYAKLDIDPDKYFESFLGMNIFGTDYSFNKLRLPVNKTDWVRHARPAIVNAFYSSLENSIQFPAGILQGHFFNAQRPKYMNFGAIGYVIGHEITHGFDDQGRQFDVKGNLRDWWHPDTQKAYLAKAKCIIEQYGNYTERATGLNLNGINTQGENIADNGGVKESYIAYRRWAEKHGPEAKLPGLDYTPEQMFWVAAGQTWCAKYRKESLKMRITTGVHSPSEFRVLGSLSNMKDFAKDFHC | ||||||
Disulfide bond | 115↔719 | |||||
Sequence: CGTYLEEENIPDDKVSISTFSVISDKLQEQLKDIITAERPETEPKHFRLPNLLYKACMNKTLIETLGPEPITRVAERLGGWPLIKGDSWNADDSWTWQEQVKKFRTAGFSMDYIIDFSIGVDLQNSTKRLIDLDQSSLALSREYLVKGFNETLVTAYYKYMVDIAVLFGANRDLAKTELLLSLEFEMALANISWPNEKRRNSSELYNLRTPAQLQAAYPYVQWVDYMNALLPEGLNVAEDEMINLSVPSFFEDLGKLLAKTPKRVIANYMFWRIHGFSVGFLSEEFRKRQLQYATALSGRQEQEARWKECVDIATSSMDEVCEDDFDSLGISVGSLYVGKHFHKDSKANALEMVNEIRNVFNDILDEVNWMDAKTKKEAKLKLHSMATHIGYPDEMLDNEKLAAYYAKLDIDPDKYFESFLGMNIFGTDYSFNKLRLPVNKTDWVRHARPAIVNAFYSSLENSIQFPAGILQGHFFNAQRPKYMNFGAIGYVIGHEITHGFDDQGRQFDVKGNLRDWWHPDTQKAYLAKAKCIIEQYGNYTERATGLNLNGINTQGENIADNGGVKESYIAYRRWAEKHGPEAKLPGLDYTPEQMFWVAAGQTWC | ||||||
Disulfide bond | 171↔424 | |||||
Sequence: CMNKTLIETLGPEPITRVAERLGGWPLIKGDSWNADDSWTWQEQVKKFRTAGFSMDYIIDFSIGVDLQNSTKRLIDLDQSSLALSREYLVKGFNETLVTAYYKYMVDIAVLFGANRDLAKTELLLSLEFEMALANISWPNEKRRNSSELYNLRTPAQLQAAYPYVQWVDYMNALLPEGLNVAEDEMINLSVPSFFEDLGKLLAKTPKRVIANYMFWRIHGFSVGFLSEEFRKRQLQYATALSGRQEQEARWKEC | ||||||
Glycosylation | 173 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 239 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 264 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 305 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 315 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 358 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 554 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 646↔771 | |||||
Sequence: CIIEQYGNYTERATGLNLNGINTQGENIADNGGVKESYIAYRRWAEKHGPEAKLPGLDYTPEQMFWVAAGQTWCAKYRKESLKMRITTGVHSPSEFRVLGSLSNMKDFAKDFHCPEGSPMNPVQKC | ||||||
Glycosylation | 653 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
N-glycosylated.
The soluble form is probably produced by proteolytic cleavage.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Detected in the stellate cells in the main segment and the bar-shaped cells in the initial segment of male and female Malpighian tubules (at protein level) (PubMed:15554877).
Expressed in the spermatheca (at protein level) (PubMed:24395329).
Expressed in the somatic cyst cells of the testes, with increased expression at the tail end of elongating cysts (PubMed:15554877, PubMed:24395329).
Expressed in the ovaries with strong expression in the posterior polar cells and in border cells of stage 8, 9, and 10 follicles (PubMed:24395329).
In adults and third-instar larvae, expressed in the brain, ventral ganglion, and stellate cells (PubMed:24395329).
Also expressed in the foregut and the imaginal disks (eye, antennal and leg) of third-instar larvae (PubMed:24395329).
In stage 17 embryos, expressed in the tracheal system, foregut, hindgut and epidermis (PubMed:24395329).
Also expressed in the stellate cell progenitors of the caudal visceral mesoderm in embryos (PubMed:17157960).
Expressed in the spermatheca (at protein level) (PubMed:24395329).
Expressed in the somatic cyst cells of the testes, with increased expression at the tail end of elongating cysts (PubMed:15554877, PubMed:24395329).
Expressed in the ovaries with strong expression in the posterior polar cells and in border cells of stage 8, 9, and 10 follicles (PubMed:24395329).
In adults and third-instar larvae, expressed in the brain, ventral ganglion, and stellate cells (PubMed:24395329).
Also expressed in the foregut and the imaginal disks (eye, antennal and leg) of third-instar larvae (PubMed:24395329).
In stage 17 embryos, expressed in the tracheal system, foregut, hindgut and epidermis (PubMed:24395329).
Also expressed in the stellate cell progenitors of the caudal visceral mesoderm in embryos (PubMed:17157960).
Gene expression databases
Interaction
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for compositional bias, region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 50-76 | Polar residues | ||||
Sequence: SNPQATALHGDSTTINQVPTGTASKGK | ||||||
Region | 50-79 | Disordered | ||||
Sequence: SNPQATALHGDSTTINQVPTGTASKGKSGD | ||||||
Domain | 83-774 | Peptidase M13 | ||||
Sequence: VCLTQECIHTASTVLRKMKPEVEPCDNFYEFACGTYLEEENIPDDKVSISTFSVISDKLQEQLKDIITAERPETEPKHFRLPNLLYKACMNKTLIETLGPEPITRVAERLGGWPLIKGDSWNADDSWTWQEQVKKFRTAGFSMDYIIDFSIGVDLQNSTKRLIDLDQSSLALSREYLVKGFNETLVTAYYKYMVDIAVLFGANRDLAKTELLLSLEFEMALANISWPNEKRRNSSELYNLRTPAQLQAAYPYVQWVDYMNALLPEGLNVAEDEMINLSVPSFFEDLGKLLAKTPKRVIANYMFWRIHGFSVGFLSEEFRKRQLQYATALSGRQEQEARWKECVDIATSSMDEVCEDDFDSLGISVGSLYVGKHFHKDSKANALEMVNEIRNVFNDILDEVNWMDAKTKKEAKLKLHSMATHIGYPDEMLDNEKLAAYYAKLDIDPDKYFESFLGMNIFGTDYSFNKLRLPVNKTDWVRHARPAIVNAFYSSLENSIQFPAGILQGHFFNAQRPKYMNFGAIGYVIGHEITHGFDDQGRQFDVKGNLRDWWHPDTQKAYLAKAKCIIEQYGNYTERATGLNLNGINTQGENIADNGGVKESYIAYRRWAEKHGPEAKLPGLDYTPEQMFWVAAGQTWCAKYRKESLKMRITTGVHSPSEFRVLGSLSNMKDFAKDFHCPEGSPMNPVQKCEVW |
Sequence similarities
Belongs to the peptidase M13 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
A0A0B4K692-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- NameB
- Length774
- Mass (Da)88,125
- Last updated2015-04-01 v1
- Checksum7E00BC75EF4472E4
A0A0B4K692-2
- NameA
- SynonymsC
- Differences from canonical
- 432-442: Missing
Features
Showing features for compositional bias, alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 50-76 | Polar residues | ||||
Sequence: SNPQATALHGDSTTINQVPTGTASKGK | ||||||
Alternative sequence | VSP_059155 | 432-442 | in isoform A | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AE014297 EMBL· GenBank· DDBJ | AAF52100.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AE014297 EMBL· GenBank· DDBJ | AFH06233.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AE014297 EMBL· GenBank· DDBJ | AGB95643.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF132153 EMBL· GenBank· DDBJ | AAD34741.1 EMBL· GenBank· DDBJ | mRNA | ||
BT120170 EMBL· GenBank· DDBJ | ADB91418.1 EMBL· GenBank· DDBJ | mRNA |